Dementia in Latin America : paving the way towards a regional action plan

Regional challenges faced by Latin American and Caribbean countries (LACs) to fight dementia, such as heterogeneity, diversity, political instabilities, and socioeconomic disparities, can be addressed more effectively grounded in a collaborative setting based on the open exchange of knowledge. In this work, the Latin American and Caribbean Consortium on Dementia (LAC-CD) proposes an agenda for integration to deliver a Knowledge to Action Framework (KtAF). First, we summarize evidence-based strategies (epidemiology, genetics, biomarkers, clinical trials, nonpharmacological interventions, networking and translational research) and align them to current global strategies to translate regional knowledge into actions with transformative power. Then, by characterizing genetic isolates, admixture in populations, environmental factors, and barriers to effective interventions and mapping these to the above challenges, we provide the basic mosaics of knowledge that will pave the way towards a KtAF. We describe strategies supporting the knowledge creation stage that underpins the translational impact of KtAF

Volumetric Brain Changes In Thalamus, Corpus Callosum And Medial Temporal Structures: Mild Alzheimer's Disease Compared With Amnestic Mild Cognitive Impairment.

It is widely known that atrophy of medial temporal structures is present in the mild stage of Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI). However, structures such as the thalamus and corpus callosum are much less studied. We compared the volumes of the entorhinal cortex, hippocampus, thalamus and the corpus callosum in 14 controls, 14 patients with mild AD and 15 with aMCI and correlated these volumes with neuropsychological data. MRI was obtained at 2 T followed by manual segmentation. We found atrophy in hippocampi and thalami of MCI patients compared to controls, and in the bilateral entorhinal cortex of aMCI compared to AD patients. All the structures showed atrophy in AD patients compared to controls, including the corpus callosum. Our study confirms that thalamic areas are atrophied in aMCI, and the corpus callosum might represent a good structural marker for mild AD. Those areas were associated with cognitive functions already described in the literature.34149-5

Structural Connectivity Of The Default Mode Network And Cognition In Alzheimer׳s Disease.

Disconnectivity between the Default Mode Network (DMN) nodes can cause clinical symptoms and cognitive deficits in Alzheimer׳s disease (AD). We aimed to examine the structural connectivity between DMN nodes, to verify the extent in which white matter disconnection affects cognitive performance. MRI data of 76 subjects (25 mild AD, 21 amnestic Mild Cognitive Impairment subjects and 30 controls) were acquired on a 3.0T scanner. ExploreDTI software (fractional Anisotropy threshold=0.25 and the angular threshold=60°) calculated axial, radial, and mean diffusivities, fractional anisotropy and streamline count. AD patients showed lower fractional anisotropy (P=0.01) and streamline count (P=0.029), and higher radial diffusivity (P=0.014) than controls in the cingulum. After correction for white matter atrophy, only fractional anisotropy and radial diffusivity remained significantly lower in AD compared to controls (P=0.003 and P=0.05). In the parahippocampal bundle, AD patients had lower mean and radial diffusivities (P=0.048 and P=0.013) compared to controls, from which only radial diffusivity survived for white matter adjustment (P=0.05). Regression models revealed that cognitive performance is also accounted for by white matter microstructural values. Structural connectivity within the DMN is important to the execution of high-complexity tasks, probably due to its relevant role in the integration of the network.22315-2

Effects of task complexity on activation of language areas in a semantic decision FMRI protocol

Language tasks used for clinical fMRI studies may be too complex for some patients with cognitive impairments, and easier versions are sometimes substituted, though the effects on brain activity of such changes in task complexity are largely unknown. To investigate these differences, we compared two versions of an fMRI language comprehension protocol, with different levels of difficulty, in 24 healthy right-handed adults. The protocol contrasted an auditory word comprehension task (semantic decision) with a nonspeech control task using tone sequences (tone decision). In the complex version (CV), the semantic decision task required two complex semantic decisions for each word, and the tone decision task required the participant to count the number of target tones in each sequence. In the easy version (EV), the semantic task required only a single easier decision, and the tone task required only detection of the presence or absence of a target tone in each sequence. The protocols were adapted for a Brazilian population. Typical left hemisphere language lateralization was observed in 92% of participants for both CV and EV using the whole-brain lateralization index, and typical language lateralization was also observed for others regions of interest. Task performance was superior on the EV compared to the CV (p=0.014). There were many common areas of activation across the two version; however, the CV produced greater activation in the left superior and middle frontal giri, angular gyrus, and left posterior cingulate gyrus compared to the EV, the majority of which are areas previously identified with language and semantic processing. The EV produced stronger activation only in a small area in the posterior middle temporal gyrus. These results reveal differences between two versions of the protocol and provide evidence that both are useful for language lateralization and worked well for Brazilian population. The complex version produces stronger activation in several nodes of the semantic network and therefore is elected for participants who can perform well these tasks.Language tasks used for clinical fMRI studies may be too complex for some patients with cognitive impairments, and "easier" versions are sometimes substituted, though the effects on brain activity of such changes in task complexity are largely unknown. To81140148FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR2012/05364-8, 2013/07559-3EX17229/12-

Hippocampal atrophy disrupts the language network but not hemispheric language lateralization

Objective: It is still unclear how temporal lobe epilepsy (TLE) with and without hippocampal atrophy (HA) affects cortical language distribution. We aimed to investigate the role of the hippocampus on language lateralization, activation pattern, and functional connectivity (FC) in patients with TLE. Methods: We investigated 93 patients with TLE-divided into right HA (RHA), left HA (LHA), and negative magnetic resonance imaging (MRI) (non-HA)-and 101 controls using a semantic-language functional MRI (fMRI) task and the Boston Naming Test (BNT). Results: Groups did not differ in the frequency of atypical language lateralization (LL), which correlated differently with handedness in each brain region and group. Blood-oxygen-level dependend (BOLD) activation patterns and region of interest (ROI)-to-ROI FC differed between LHA and controls, as well as between LHA and non-HA patients. In the task activation pattern analysis, there was a decrease in the activation of patients with LHA relative to controls, exactly in the left hippocampus. However, non-HA patients had increased FC relative to controls in the left superior temporal gyrus region. Seed-to-voxel FC demonstrated greater differences between patients and controls and smaller differences among patient groups. The non-HA group was similar to controls, except for increased BOLD activation and increase FC in the superior temporal gyri. RHA and LHA differed from controls in BNT. BNT correlated with fMRI activation in RHA and non-HA groups. Significance: LHA affected naming performance, fMRI semantic task activation pattern, and FC more than RHA and non-HA. Contrary to our expectations, LHA did not increase the frequency of atypical LL. Regardless of the side, HA impacts negatively on the language network but not on hemispheric language lateralization.604744755COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPBEX17229/12-02012/05364-8; 2013/07559-

Effects of task complexity on activation of language areas in a semantic decision fMRI protocol

a b s t r a c t Language tasks used for clinical fMRI studies may be too complex for some patients with cognitive impairments, and "easier" versions are sometimes substituted, though the effects on brain activity of such changes in task complexity are largely unknown. To investigate these differences, we compared two versions of an fMRI language comprehension protocol, with different levels of difficulty, in 24 healthy right-handed adults. The protocol contrasted an auditory word comprehension task (semantic decision) with a nonspeech control task using tone sequences (tone decision). In the "complex" version (CV), the semantic decision task required two complex semantic decisions for each word, and the tone decision task required the participant to count the number of target tones in each sequence. In the "easy" version (EV), the semantic task required only a single easier decision, and the tone task required only detection of the presence or absence of a target tone in each sequence. The protocols were adapted for a Brazilian population. Typical left hemisphere language lateralization was observed in 92% of participants for both CV and EV using the whole-brain lateralization index, and typical language lateralization was also observed for others regions of interest. Task performance was superior on the EV compared to the CV (p¼ 0.014). There were many common areas of activation across the two version; however, the CV produced greater activation in the left superior and middle frontal giri, angular gyrus, and left posterior cingulate gyrus compared to the EV, the majority of which are areas previously identified with language and semantic processing. The EV produced stronger activation only in a small area in the posterior middle temporal gyrus. These results reveal differences between two versions of the protocol and provide evidence that both are useful for language lateralization and worked well for Brazilian population. The complex version produces stronger activation in several nodes of the semantic network and therefore is elected for participants who can perform well these tasks

Neuropsychiatric symptoms in the prodromal stages of dementia

Purpose of reviewTo critically discuss the neuropsychiatric symptoms in the prodromal stages of dementia in order to improve the early clinical diagnosis of cognitive and functional deterioration.Recent findingsCurrent criteria for cognitive syndrome, including Alzheimer's disease, comprise the neuropsychiatric symptoms in addition to cognitive and functional decline. Although there is growing evidence that neuropsychiatric symptoms may precede the prodromal stages of dementia, these manifestations have received less attention than traditional clinical hallmarks such as cognitive and functional deterioration. Depression, anxiety, apathy, irritability, agitation, sleep disorders, among other symptoms, have been hypothesized to represent a prodromal stage of dementia or, at least, they increase the risk for conversion from minor neurocognitive disorder to major neurocognitive disorder. Longitudinal investigations have provided increased evidence of progression to dementia in individuals with minor neurocognitive disorder when neuropsychiatric symptoms also were present.SummaryAlthough neuropsychiatric symptoms are strongly associated with a higher risk of cognitive and functional deterioration, frequently the clinician does not acknowledge these conditions as increasing the risk of dementia. When the clinician accurately diagnoses neuropsychiatric symptoms in the prodromal stage of dementia, he could early establish appropriate treatment and, may be, delay the beginning of clinical and functional deterioration

Cortical correlates of affective syndrome in dementia due to Alzheimer’s disease

Neuropsychiatric symptoms in Alzheimer’s disease (AD) are prevalent, however their relationship with patterns of cortical atrophy is not fully known. Objectives To compare cortical atrophy’s patterns between AD patients and healthy controls; to verify correlations between neuropsychiatric syndromes and cortical atrophy. Method 33 AD patients were examined by Neuropsychiatric Inventory (NPI). Patients and 29 controls underwent a 3T MRI scanning. We considered four NPI syndromes: affective, apathy, hyperactivity and psychosis. Correlations between structural imaging and neuropsychiatric scores were performed by Freesurfer. Results were significant with a p-value < 0.05, corrected for multiple comparisons. Results Patients exhibited atrophy in entorhinal cortices, left inferior and middle temporal gyri, and precuneus bilaterally. There was correlation between affective syndrome and cortical thickness in right frontal structures, insula and temporal pole. Conclusion Cortical thickness measures revealed atrophy in mild AD. Depression and anxiety symptoms were associated with atrophy of right frontal, temporal and insular cortices.Os sintomas neuropsiquiátricos na doença de Alzheimer (DA) são prevalentes, porém suas relações com padrões de atrofia cortical não são totalmente compreendidas. Objetivos Comparar padrões de atrofia cortical entre DA e controles; verificar se há correlações entre sintomas neuropsiquiátricos e atrofia cortical. Método 33 pacientes com DA foram examinados pelo Inventário Neuropsiquiátrico. Os pacientes e 29 controles foram submetidos à RNM. Consideramos quatro síndromes: afetiva, apatia, hiperatividade e psicose. Correlações entre imagens estruturais e os scores foram feitas pelo Freesurfer. Os resultados foram significantes com um valor de p < 0,05, corrigido para múltiplas comparações. Resultados Pacientes exibiram atrofia nos córtices entorrinais, giros temporal médio e inferior esquerdos, e precuneo bilateralmente. Houve correlação entre síndrome afetiva e espessura cortical em estruturais frontais direitas, ínsula e polo temporal. Conclusão Medidas de espessura cortical revelaram atrofia na DA. Sintomas de depressão e ansiedade foram associados à atrofia dos córtices frontal direito, temporal e ínsula.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP